scholarly journals Towards Biophysical Markers of Depression Vulnerability

2021 ◽  
Author(s):  
D.A. Pinotsis ◽  
S. Fitzgerald ◽  
C. See ◽  
A. Sementsova ◽  
A. S. Widge

AbstractA major difficulty with treating psychiatric disorders is their heterogeneity: different neural causes can lead to the same phenotype. To address this, we propose describing the underlying pathophysiology in terms of interpretable, biophysical parameters of a neural model derived from the electroencephalogram. We analyzed data from a small patient cohort of patients with depression and controls. We constructed biophysical models that describe neural dynamics in a cortical network activated during a task that is used to assess depression state. We show that biophysical model parameters are biomarkers, that is, variables that allow subtyping of depression at a biological level. They yield a low dimensional, interpretable feature space that allowed description of differences between individual patients with depressive symptoms. They capture internal heterogeneity/variance of depression state and achieve significantly better classification than commonly used EEG features. Our work is a proof of concept that a combination of biophysical models and machine learning may outperform earlier approaches based on classical statistics and raw brain data.

2019 ◽  
Author(s):  
Griffin Chure ◽  
Manuel Razo-Mejia ◽  
Nathan M. Belliveau ◽  
Tal Einav ◽  
Zofii A. Kaczmarek ◽  
...  

Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response. We find the energetic effects of the mutations can be categorized into several classes which have characteristic curves as a function of the inducer concentration. We experimentally test these diagnostic predictions using the well-characterized LacI repressor of Escherichia coli, probing several mutations in the DNA binding and inducer binding domains. We find that the change in gene expression due to a point mutation can be captured by modifying only a subset of the model parameters that describe the respective domain of the wild-type protein. These parameters appear to be insulated, with mutations in the DNA binding domain altering only the DNA affinity and those in the inducer binding domain altering only the allosteric parameters. Changing these subsets of parameters tunes the free energy of the system in a way that is concordant with theoretical expectations. Finally, we show that the induction profiles and resulting free energies associated with pairwise double mutants can be predicted with quantitative accuracy given knowledge of the single mutants, providing an avenue for identifying and quantifying epistatic interactions.SummaryWe present a biophysical model of allosteric transcriptional regulation that directly links the location of a mutation within a repressor to the biophysical parameters that describe its behavior. We explore the phenotypic space of a repressor with mutations in either the inducer binding or DNA binding domains. Using the LacI repressor in E. coli, we make sharp, falsifiable predictions and use this framework to generate a null hypothesis for how double mutants behave given knowledge of the single mutants. Linking mutations to the parameters which govern the system allows for quantitative predictions of how the free energy of the system changes as a result, permitting coarse graining of high-dimensional data into a single-parameter description of the mutational consequences.


2014 ◽  
Vol 143 (3) ◽  
pp. 401-416 ◽  
Author(s):  
Keegan E. Hines ◽  
Thomas R. Middendorf ◽  
Richard W. Aldrich

A major goal of biophysics is to understand the physical mechanisms of biological molecules and systems. Mechanistic models are evaluated based on their ability to explain carefully controlled experiments. By fitting models to data, biophysical parameters that cannot be measured directly can be estimated from experimentation. However, it might be the case that many different combinations of model parameters can explain the observations equally well. In these cases, the model parameters are not identifiable: the experimentation has not provided sufficient constraining power to enable unique estimation of their true values. We demonstrate that this pitfall is present even in simple biophysical models. We investigate the underlying causes of parameter non-identifiability and discuss straightforward methods for determining when parameters of simple models can be inferred accurately. However, for models of even modest complexity, more general tools are required to diagnose parameter non-identifiability. We present a method based in Bayesian inference that can be used to establish the reliability of parameter estimates, as well as yield accurate quantification of parameter confidence.


2019 ◽  
Vol 29 (07) ◽  
pp. 1850058 ◽  
Author(s):  
Juan M. Górriz ◽  
Javier Ramírez ◽  
F. Segovia ◽  
Francisco J. Martínez ◽  
Meng-Chuan Lai ◽  
...  

Although much research has been undertaken, the spatial patterns, developmental course, and sexual dimorphism of brain structure associated with autism remains enigmatic. One of the difficulties in investigating differences between the sexes in autism is the small sample sizes of available imaging datasets with mixed sex. Thus, the majority of the investigations have involved male samples, with females somewhat overlooked. This paper deploys machine learning on partial least squares feature extraction to reveal differences in regional brain structure between individuals with autism and typically developing participants. A four-class classification problem (sex and condition) is specified, with theoretical restrictions based on the evaluation of a novel upper bound in the resubstitution estimate. These conditions were imposed on the classifier complexity and feature space dimension to assure generalizable results from the training set to test samples. Accuracies above [Formula: see text] on gray and white matter tissues estimated from voxel-based morphometry (VBM) features are obtained in a sample of equal-sized high-functioning male and female adults with and without autism ([Formula: see text], [Formula: see text]/group). The proposed learning machine revealed how autism is modulated by biological sex using a low-dimensional feature space extracted from VBM. In addition, a spatial overlap analysis on reference maps partially corroborated predictions of the “extreme male brain” theory of autism, in sexual dimorphic areas.


2021 ◽  
Author(s):  
Rogini Runghen ◽  
Daniel B Stouffer ◽  
Giulio Valentino Dalla Riva

Collecting network interaction data is difficult. Non-exhaustive sampling and complex hidden processes often result in an incomplete data set. Thus, identifying potentially present but unobserved interactions is crucial both in understanding the structure of large scale data, and in predicting how previously unseen elements will interact. Recent studies in network analysis have shown that accounting for metadata (such as node attributes) can improve both our understanding of how nodes interact with one another, and the accuracy of link prediction. However, the dimension of the object we need to learn to predict interactions in a network grows quickly with the number of nodes. Therefore, it becomes computationally and conceptually challenging for large networks. Here, we present a new predictive procedure combining a graph embedding method with machine learning techniques to predict interactions on the base of nodes' metadata. Graph embedding methods project the nodes of a network onto a---low dimensional---latent feature space. The position of the nodes in the latent feature space can then be used to predict interactions between nodes. Learning a mapping of the nodes' metadata to their position in a latent feature space corresponds to a classic---and low dimensional---machine learning problem. In our current study we used the Random Dot Product Graph model to estimate the embedding of an observed network, and we tested different neural networks architectures to predict the position of nodes in the latent feature space. Flexible machine learning techniques to map the nodes onto their latent positions allow to account for multivariate and possibly complex nodes' metadata. To illustrate the utility of the proposed procedure, we apply it to a large dataset of tourist visits to destinations across New Zealand. We found that our procedure accurately predicts interactions for both existing nodes and nodes newly added to the network, while being computationally feasible even for very large networks. Overall, our study highlights that by exploiting the properties of a well understood statistical model for complex networks and combining it with standard machine learning techniques, we can simplify the link prediction problem when incorporating multivariate node metadata. Our procedure can be immediately applied to different types of networks, and to a wide variety of data from different systems. As such, both from a network science and data science perspective, our work offers a flexible and generalisable procedure for link prediction.


2021 ◽  
Vol 50 (1) ◽  
pp. 138-152
Author(s):  
Mujeeb Ur Rehman ◽  
Dost Muhammad Khan

Recently, anomaly detection has acquired a realistic response from data mining scientists as a graph of its reputation has increased smoothly in various practical domains like product marketing, fraud detection, medical diagnosis, fault detection and so many other fields. High dimensional data subjected to outlier detection poses exceptional challenges for data mining experts and it is because of natural problems of the curse of dimensionality and resemblance of distant and adjoining points. Traditional algorithms and techniques were experimented on full feature space regarding outlier detection. Customary methodologies concentrate largely on low dimensional data and hence show ineffectiveness while discovering anomalies in a data set comprised of a high number of dimensions. It becomes a very difficult and tiresome job to dig out anomalies present in high dimensional data set when all subsets of projections need to be explored. All data points in high dimensional data behave like similar observations because of its intrinsic feature i.e., the distance between observations approaches to zero as the number of dimensions extends towards infinity. This research work proposes a novel technique that explores deviation among all data points and embeds its findings inside well established density-based techniques. This is a state of art technique as it gives a new breadth of research towards resolving inherent problems of high dimensional data where outliers reside within clusters having different densities. A high dimensional dataset from UCI Machine Learning Repository is chosen to test the proposed technique and then its results are compared with that of density-based techniques to evaluate its efficiency.


2018 ◽  
Author(s):  
Elizabeth Huber ◽  
Rafael Neto Henriques ◽  
Julia P. Owen ◽  
Ariel Rokem ◽  
Jason D. Yeatman

AbstractDiffusion MRI (dMRI) holds great promise for illuminating the biological changes that underpin cognitive development. The diffusion of water molecules probes the cellular structure of brain tissue, and biophysical modeling of the diffusion signal can be used to make inferences about specific tissue properties that vary over development or predict cognitive performance. However, applying these models to study development requires that the parameters can be reliably estimated given the constraints of data collection with children. Here we collect repeated scans using a multi-shell diffusion MRI protocol in a group of children (ages 7-12) and use two popular biophysical models to characterize axonal properties. We first assess the scan-rescan reliability of model parameters and show that axon water faction can be reliably estimated from a relatively fast acquisition, without applying spatial smoothing or de-noising. We then investigate developmental changes in the white matter, and individual differences in white matter that correlate with reading skill. Specifically, we test the hypothesis that previously reported correlations between reading skill and diffusion anisotropy in the corpus callosum reflect increased axon density in poor readers. Both models support this interpretation, highlighting the utility of biophysical models for testing specific hypotheses about cognitive development.


2016 ◽  
Vol 800 ◽  
pp. 72-110 ◽  
Author(s):  
Richard Semaan ◽  
Pradeep Kumar ◽  
Marco Burnazzi ◽  
Gilles Tissot ◽  
Laurent Cordier ◽  
...  

We propose a hierarchy of low-dimensional proper orthogonal decomposition (POD) models for the transient and post-transient flow around a high-lift airfoil with unsteady Coanda blowing over the trailing edge. The modal expansion comprises actuation modes as a lifting method for wall actuation following Graham et al. (Intl J. Numer. Meth. Engng, vol. 44 (7), 1999, pp. 945–972) and Kasnakoğlu et al. (Intl J. Control, vol. 81 (9), 2008, pp. 1475–1492). A novel element is separate actuation modes for different frequencies. The structure of the dynamic model rests on a Galerkin projection using the Navier–Stokes equations, simplifying mean-field considerations, and a stochastic term representing the background turbulence. The model parameters are identified with a data assimilation (4D-Var) method. We propose a model hierarchy from a linear oscillator explaining the suppression of vortex shedding by blowing to a fully nonlinear model resolving unactuated and actuated transients with steady and high-frequency modulation of blowing. The models’ accuracy is assessed through the mode amplitudes and an estimator for the lift coefficient. The robustness of the model is physically justified, and then observed for the training and the validation dataset.


Author(s):  
Jodie Schlaefer ◽  
Alex Carter ◽  
Severine Choukroun ◽  
Robert Coles ◽  
Kay Critchell ◽  
...  

2011 ◽  
Vol 33 (1) ◽  
pp. 37 ◽  
Author(s):  
G. W. Fraser ◽  
J. O. Carter ◽  
G. M. McKeon ◽  
K. A. Day

Sub-daily rainfall intensity has a significant impact on runoff and erosion rates in northern Australian rangelands. However, it has been difficult to include sub-daily rainfall intensity in rangeland biophysical models using historical climate data due to the limited number of pluviograph stations with long-term records. In this paper a new empirical model (‘Temperature I15’ model) was developed to predict the daily maximum 15-min rainfall intensity (I15) using daily minimum and maximum temperature and daily rainfall totals from 12 selected pluviograph stations across Australia. The ‘Temperature I15’ model accounted for 46% (P < 0.01) of the variation in observed daily I15 for an independent validation dataset derived from 67 Australia-wide pluviograph stations and represented both geographical and seasonal variability in I15. The model also accounted for 70% (P < 0.01) of the variation in the observed historical trend in I15 for the full record period (average record period was 37 years) of 73 Australia-wide pluviograph stations. The ‘Temperature I15’ model was found to be an improvement on a past empirical model of I15 and can be easily implemented in biophysical models by using readily available daily climate data. However, as the ‘Temperature I15’ model only represented 46% of the variation in daily observed I15, the model is best used in simulation studies on ‘timeframes’ in excess of 5 years. The new ‘Temperature I15’ model was implemented in the runoff equation of the Australia-wide spatial pasture growth model AussieGRASS, which predicts daily water balance and pasture growth for 185 different pasture communities. This resulted in an improved simulation of green cover for 71% of pasture communities but was worse for 25% of communities, with no change for 4% of communities.


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